Retinoic acid and dexamethasone affect RAR-beta and surfactant protein C mRNA in the MLE lung cell line.
Lung development and surfactant biosynthesis are affected by retinoic acid (RA) and dexamethasone (Dex). Using a mouse lung epithelial cell line, we are exploring RA-Dex interactions through the study of RA and Dex effects on RA receptor (RAR) and surfactant protein (SP) C mRNA expression. RA increased expression of RAR-beta (5.5 times) and SP-C (2 times) mRNA, with maximal effects at 24 h and at 10(-6) M. The RA induction was not inhibited by cycloheximide, suggesting RA affects transcription. With added actinomycin D, RA did not affect the disappearance rate of RAR-beta mRNA, but SP-C mRNA degradation was slowed, indicating an effect on SP-C mRNA stability. Dex decreased RAR-beta and SP-C expression to 75 and 70% of control values, respectively, with greatest effects at 48 h and at 10(-7) M. There was no effect of Dex on either RAR-beta or SP-C mRNA disappearance with actinomycin D. However, cycloheximide prevented the effect of Dex. Despite Dex, RA increased both RAR-beta and SP-C mRNA. This work suggests that RA and Dex affect RAR-beta and SP-C genes by different mechanisms.
Grummer
M A
MA
Department of Pediatrics, Meriter Hospital Perinatal Center, University of Wisconsin, Madison 53715, USA.
Zachman
R D
RD
D000818:Animals; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D007700:Kinetics; D008168:Lung; D051379:Mice; D011510:Proteolipids / Q000096:biosynthesis*; D011663:Pulmonary Surfactants / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis*; D014158:Transcription, Genetic / Q000187:drug effects*; D014212:Tretinoin / Q000494:pharmacology*
D011510:Proteolipids; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; C082925:retinoic acid receptor beta; D003609:Dactinomycin; D014212:Tretinoin; D003907:Dexamethasone; D003513:Cycloheximide